In many cases, it is much more efficient to screen as mixtures because it pares down the dataset to a manageable range. One uses screening mixtures by soaking the crystal in a cocktail with multiple ligands. The secret to designing the proper mixture is to ensure that each ligand in the cocktail is differentiable from the other ligands, even at low resolutions. Express-Zen-Core288™ has a very high shape diversity, making it possible to group into shape diverse mixtures that can be distinguished at 2.7Å-3.0Å.
How Does Zenobia Make it's Mixtures?
Zenobia's mixtures for crystallographic screening contain up to 6 compounds that are highly shape diverse permitting identification of the hit from the shape of the electron density map (Nienaber et al., 2000). For those that are not limited by crystals or beamtime, mixtures of 3 or single compound screening kits are also available for crystallography. Sample mixtures of 6 are depicted below.
Crystallographic screening is a method used to detect ligands that bind to a target protein. What makes this metod special is that it also provides structural data about the binding location and interactions between the ligand and protein. The crystal itself has the protein molecules lined up in an ordered array with large solvent channels so that ligands can soak in and bind to sites on the crystallized protein. This method is exceptionally successful in detecting weakly binding ligands because the protein is highly concentrated in the crystal. Once the crystal has been soaked in the cocktail of ligands, diffraction data are collected and used to calculate an electron density map to determine if any of the ligands bound to the protein. If they do bind, one can tell by a visible positive electron density peak in a difference density map between the putative ligand protein complex and apoprotein. The ligand cocktails should be designed so that each lig...
As fragment screening continues to grow in popularity and establish itself as an integral part of discovery research, the emergence of more and more compounds added to fragment library collections seems to grow exponentially. What once was an efficient means of effectively screening a target to provide information about its drugability or identify the unique building blocks of a clinical candidate, has now become diluted in a pool of tens or hundreds of thousands of compounds to endlessly screen.
Designing efficiency into any application should be one of the primary principles and only be modified when expanded scope adds additional information. When this simple required element is ignored or modified to adapt to an ever changing landscape of discovery research, the other primary principle that appears to be compromised is value. Value is the true measurement of success. The simplicity of design directly relates to the elegance of its footprint, regardless of its true complexity, an...
Welcome to our new blog. Here, we will be sharing thoughts and opinions based upon our 20-30 years of experience in fragment screening and structural biology. We will share data we have generated and significant findings that we feel apply to the structural biology and fragment screening field. We welcome your comments on the utility of our products, challenges you face in your research and your opionions on the field in general.
Zenobia Fragments became an official entity in 2013 as a forum for the growing products division of Zenobia Therapeutics (founded in 2008).
Our mission is to provide cutting edge products based on our experience and internal research. We provide products we have developed to accelerate Zenobia Therapeutics research and products developed and tested at Zenobia Fragments. By providing these products, we hope to advance research around the world and facilitate discovery of new treatments for unmet medical needs.